According to the American Diabetes Association, over 6% of the US population is affected by diabetes. Worldwide, the number of people with diabetes is increasing at an astounding rate and is predicted reach epidemic proportions. Commercially available methods of monitoring glucose levels are invasive and prone to error. For many individuals, monitoring must be performed frequently throughout the day. The pain and risk of infection from invasive probes can often deter them from maintaining their prescribed monitoring schedule, escalating the risks of secondary aliments of diabetes mellitus. It would be desirable to alleviate the pain and risks for individuals who must routinely monitor their body chemistry by developing a device that accurately characterizes aqueous biological samples, such as urine, blood, saliva, or other bodily fluids, in a non-invasive manner. Current research has focused on optical identification of glucose levels in urine within the short-wavelength near infrared (sw-NIR) spectrum.
Noninvasive analyte monitoring using optical techniques are well known in the prior art. For example, U.S. Pat. No. 6,377,828 issued Apr. 23, 2002, to Chaiken discloses using the Raman spectra emitted by a tissue after excitation with a first wavelength equal to the absorption frequency of a temperature probe, hemoglobin, and a second wavelength equal to the absorption frequency of the analyte, in order to measure blood glucose concentrations. U.S. Pat. No. 6,640,116 issued Oct. 28, 2003, to Diab discloses use of Faraday rotation measurements (polarization of the incident beam by a magnetic field) through tissue for glucose measurement. Also, U.S. Pat. No. 6,445,938 issued Sep. 3, 2002, to Berman et al discloses a device that uses attenuated total reflection (ATR) infrared spectroscopy on the patient's fingertip for monitoring glucose levels in the body based on analyses of unique IR signatures.
It has also been known to provide an implantable light sensor in vivo for monitoring blood glucose levels. For example, U.S. Pat. No. 6,122,536 issued Sep. 19, 2000, to Sun, et al. discloses an infrared light sensor surgically implanted around a blood vessel, puncturing each side of the vessel, for continuously monitoring a blood constituent such as glucose by discriminating among different spectral bands having a unique temporal or frequency modulation. U.S. Pat. No. 6,097,975 issued Aug. 1, 2000, to Petrovsky, et al. measures blood glucose concentration by projecting a pulse of light through an optical fiber onto a blood-vessel-rich area of the body (such as the inner wrist, elbow or ear lobe). U.S. Pat. No. 6,016,435 issued Jan. 18, 2000, to Maruo, et al. discloses the analysis of NIR light received in a light-receiving unit positioned in the) dermis layer of skin, based on statistically correlating glucose concentration detected in the dermis region with that of test subjects.
Other prior art involving the use of light in the near-infrared (NIR) range for monitoring blood glucose concentration includes U.S. Pat. No. 5,070,874 to Barnes, et al., U.S. Pat. No. 5,360,004 to Purdy et al., and U.S. Pat. No. 5,267,152 to Yang et al. Diffusive reflectance NIR spectroscopy is also disclosed in U.S. Pat. No. 5,910,109 to Peters, et al., International Patent Publication WO 0216905, U.S. Pat. No. 6,152,876 assigned to Rio Grande Medical Technologies Inc., U.S. Pat. No. 5,945,676 assigned to Sensys Medical, and U.S. Pat. Nos. 5,086,229 and 5,028,787 to Rosenthal, et al. Spectral analysis of a polychromatic light source for noninvasive measurement of blood glucose is disclosed in U.S. Pat. No. 5,361,758 to Hall, et al.
However, such prior art devices have limitations that prevent their widespread use, e.g., lack of sensitivity and specificity, interference with other blood constituents and noise limitations. Conventional noninvasive sensor systems for blood glucose monitoring still require frequent “finger-stick” blood glucose measurements for recalibration purposes, thus defeating its purpose to replace invasive methods.
U.S. Pat. No. 5,533,509 issued Jul. 9, 1996, to Koashi, et al. teaches noninvasive blood glucose monitoring using wavelength modulated light, in which the intensity of transmitted or reflected light as well as the intensity of incident light is detected, then the ratio of the two intensities and the rate of change in the ratio with respect to the change in the wavelength are determined. The derivative of the absorption spectrum of glucose is extracted and the blood sugar of that portion based on these derivative spectra for all modulating intensities of light is detected, so that derivative data of high quality is obtained in real time without requiring computer processing. However, this system is lacking in spectral referencing to completely eliminate spectral drifting of the optical system, and in the proper rationing of higher order derivative features to provide absolute glucose concentrations in varying portions of tissues.
One of the largest obstacles in non-invasive biomedical sensing is variability in the samples from person to person and from day to day. Numerous variables must be analyzed simultaneously, requiring long and complex multivariate calculations to provide precise measurements of constituents. The primary limitation of the multivariate analysis used in conventional measurement techniques is that if one of the components is estimated incorrectly, then the whole analysis can be skewed. This inherent problem can be difficult to isolate and correct in real-time.